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Bronchial Fistula Associated with Sunitinib in a Patient Previously Treated with Radiation Therapy

Clinical Specialist, Centre Hospitalier Saint Quentin, Saint Quentin, France

Michel Andrejak, MD

Professor, Department of Research, Faculty of Medicine, Centre Hospitalier Universitaire Amiens, Amiens, France

Houcine Bentayeb, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Marc Kanaan, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Clément Fournier, MD

Clinical Specialist, Service d'Endoscopie Respiratoire, Clinique des Maladies Respiratoires, Centre Hospitalier Régional Universitaire Lille, Lille, France

Emmanuelle Lecuyer, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Marie Boutemy, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Réda Garidi, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Youcef Douadi, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Charles Dayen, MD

Clinical Specialist, Centre Hospitalier Saint Quentin

Reprints: Dr. Dayen, Centre Hospitalier Saint Quentin, Av Michel de l'Hospital, 02321 Saint Quentin, France, fax 0323067513, c.dayen{at}ch-stquentin.fr

OBJECTIVE: To report a case of bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy.

CASE SUMMARY: A 40-year-old man with renal cell cancer diagnosed in 2005 and initially treated by radical nephrectomy presented in March 2007 with a recurrence with cerebral, mediastinal, and lung metastases. A thoracic computed tomography (CT) scan showed a subcarinal tumor obstructing the bronchus intermedius. The patient was initially treated with cerebral and thoracic radiotherapy and then with sunitinib 50 mg/day (4 weeks on, 2 weeks off). Two months after the beginning of treatment, a CT scan revealed a dramatic reduction in the size of the tumor, associated with a bronchial fistula. This was confirmed by flexible bronchoscopy, which showed complete necrosis of the tumor and a large perforation of the bronchus intermedius. Sunitinib was immediately withdrawn and antibiotic prophylaxis was instituted. It was not possible to place an endobronchial stent. Two weeks later, flexible bronchoscopy revealed the reappearance of a yellowish mass protruding into the bronchus intermedius (40% obstruction). A few months later, the obstruction of the bronchus intermedius progressed to 90% and was associated with a contralateral obstruction of the left mainstem bronchus (20%). A rigid bronchoscopy was then performed to clear the obstruction and an endobronchial stent was placed, with satisfactory initial results. In February 2008, the patient presented with new bronchial obstruction under the endobronchial stent but refused a rigid bronchoscopy and died in March 2008.

DISCUSSION: Sunitinib, a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities, has been approved for the treatment of advanced renal cell carcinoma. This treatment is generally well tolerated. Serious complications may occur, however. According to the Naranjo probability scale, the bronchial fistula was possibly related to sunitinib treatment.

CONCLUSIONS: This is a rare case of a bronchial perforation leading to a fistula associated with sunitinib treatment after mediastinal radiation therapy. Clinicians may consider strict follow-up of patients with proximal lung metastases treated with sunitinib (CT scan and, if appropriate, placement of an endobronchial stent).

Key Words: adverse effect, fistula, radiotherapy, renal cell cancer, sunitinib, tumor necrosis, VEGF

Published Online, January 5, 2010. www.theannals.com, DOI 10.1345/aph.1M469